Collection, processing and purification of biological samples are important processes in a range of medical therapies and procedures. Important biological samples used as therapeutic agents include whole blood and its various purified blood components, such as red blood cells, white blood cells and plasma. In the field of transfusion medicine, one or more whole blood components are directly introduced into a patient's blood stream to replace a depleted or deficient component. Infusion of plasma-derived materials, such as blood proteins, also plays a critical role in a number of therapeutic applications. For example, plasma-derived immunoglobulin is commonly provided to supplement a patient's compromised immune system. Due to increases in the demand for purified biological samples for transfusion, infusion and transplantation therapies, substantial research efforts have been directed at improving the availability, safety and purity of biological samples used as therapeutic agents.
In conventional large scale blood collection, blood is removed from a donor or patient, separated into its various blood components via centrifugation, filtration and/or elutriation and stored in sterile containers for future infusion into a patient for therapeutic use. The separated blood components typically include fractions corresponding to red blood cells, white blood cells, platelets and plasma. Separation of blood into its components may be performed continuously during collection or may be performed subsequent to collection in batches, particularly with respect to the processing of whole blood samples. Separation of blood into its various components under highly sterile conditions is crucial for a wide variety of therapeutic applications.
Recently, apheresis blood collection techniques have been widely adopted in large scale blood collection centers wherein a selected component of blood or plurality of blood components are collected and the balance of the blood is returned to the donor during collection. In apheresis, blood is removed from a donor and immediately separated into its components by on-line blood processing methods. Typically, such on-line blood processing is provided by density centrifugation, filtration and diffusion-based separation techniques. One or more of the separated blood components are collected and stored in sterile containers, while the remaining blood components are directly recirculated to the donor. An advantage of this method is that it allows more frequent donation from an individual donor because only a selected blood component is collected and purified. For example, a donor undergoing plateletpheresis, whereby platelets are collected and the non-platelet blood components are returned to the donor, may donate blood as often as once per week.
Apheresis blood processing also plays an important role in a large number of therapeutic procedures. In these methods, blood is withdrawn from a patient undergoing therapy, separated, and a selected fraction is collected while the remainder is returned to the patient. For example, a patient may undergo leukapheresis prior to radiation therapy, whereby the white blood cell component of his blood is separated, collected and stored to avoid exposure to radiation. Alternatively, apheresis techniques may be used to perform red blood cell exchange for patients with hematological disorders such as sickle cell anemia and thalassemia, whereby the patient's red blood cell component is removed and donated packed red blood cells are provided to the patient along with his remaining blood components. Further, apheresis may be used to perform therapeutic platelet depletion for patients having thrombocytosis and therapeutic plasma exchange for patients with autoimmune diseases.
Both conventional blood collection and apheresis systems typically employ differential centrifugation methods for separating blood into its various blood components. In differential centrifugation, blood is circulated through a sterile separation chamber which is rotated at high rotational speeds about a central rotation axis. Rotation of the separation chamber creates a centrifugal force directed along rotating axes of separation oriented perpendicular to the central rotation axis of the centrifuge. The centrifugal field generated upon rotation separates particles suspended in the blood sample into discrete fractions accordingly to density. Specifically, a blood sample separates into discrete phases corresponding to a higher density fraction comprising red blood cells and a lower density fraction comprising plasma. In addition, an intermediate density fraction comprising platelets and leukocytes forms an interface layer between the red blood cells and the plasma. Descriptions of blood centrifugation devices are provided in U.S. Pat. No. 5,653,887, which is hereby incorporated in its entireties by reference to the extent it is not inconsistent with the present application.
Despite the demonstrated effectiveness of apheresis blood processing in automated blood donation and in a large number of therapies, several practical limitations remain affecting the practice of these methods. In particular, the occurrence of blood vessel infiltration caused by rapid changes in access blood vessel pressure is a common problem experienced by virtually all apheresis methods known in the art. Although the incidence of blood vessel infiltration is dependent on the particular physiology and anatomy of the subject undergoing a selected blood processing procedure, conventional apheresis systems exhibit on average an incidence of blood vessel infiltration typically greater than or equal to about 4.5%. This correspond to a very significant occurrence of infiltration; about 1 out of every 20 apheresis procedures.
During infiltration, the pressure exerted on the walls of an access blood vessel, such as an access vein, increases or decreases due to the flow of blood or blood components into or out of the subject of a blood processing procedure. To reduce the pressure, the access blood vessel may expand or contract at a rate depending on the size and elasticity of the vessel. In some instances, however, the change in pressure is too great or delivered over a very short time interval and, thus, the access blood vessel cannot accommodate the change in pressure and the change in pressure may result in blood vessel infiltration. For example, a sharp increase in blood vessel pressure over a short time may cause a perforation in the wall of the blood vessel, commonly referred to as vein “blow out.” Also, a sharp decrease in blood vessel pressure over a short time may cause the walls of the blood vessel to collapse. Finally, rapid changes in the direction of change in blood vessel pressure may also result in damage to the walls of an access blood vessel.
Blood vessel infiltration has a number of significant deleterious affects on extracorporeal blood processing. First, infiltration may cause injury to the patient or subject undergoing a blood processing procedure. For example, infiltration may result in a hematoma or a change in blood pressure. In addition, infiltration may trigger a cascade of more serious health problems, such as cardiac arrest or embolism. Second, infiltration causes serious pain for the donor or patient undergoing a blood processing procedure. This negatively impacts patient or donor satisfaction with a given blood processing procedure and may affect a donor's decision to donate blood or blood components on a regular basis. Third, infiltration results in a substantial decrease in the flow rate of blood or blood components into or out of a patient or donor. This reduction in flow results in blood processing delay or may result in termination of a selected blood processing procedure. Finally, the risk of infiltration associated with these procedures increases the need for operator or physician intervention and, thus, reduces efficiency and substantially adds to the costs of blood donation or apheresis therapies.
It will be appreciated from the foregoing that a clear need exists for methods and devices for processing blood and blood components having a reduced risk of infiltration. Specifically, apheresis methods and devices are needed which enhance patient or donor comfort and reduce the change in vein pressure experienced during removal and return of blood and blood components during extracorporeal blood processing. Finally, automated methods and devices of apheresis blood processing are needed which require less operator or physician intervention.